Gastric Bypass Surgery Improves the Skeletal Muscle Ceramide/S1P Ratio and Upregulates the AMPK/ SIRT1/ PGC-1α Pathway in Zucker Diabetic Fatty Rats

Huang, Hazel; Aminian, Ali; Hassan, Monique; Dan, Olivia; Axelrod, Christopher L.; Schauer, Philip R.; Brethauer, Stacy A.; Kirwan, John P.

doi:10.1007/s11695-019-03800-z

Cited by 15 publications

(19 citation statements)

References 51 publications

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“…In summary, we have presented further evidence against leptin being an essential mediator of the sustained weight loss, appetite suppression and improved glycemic control induced by RYGB, which instead points to additional circulating and/or neural factors. Our findings are thus consistent with the majority of previous studies in Zucker Fatty fa/fa and Zucker Diabetic Fatty fa/fa rats as models of leptin receptor deficiency [45][46][47]49,50,52,55,59,62,64], and place their findings in a new light.…”

Section: Discussionsupporting

confidence: 93%

“…With regards to improvements in glucose homeostasis induced by RYGB, we found a reduction of plasma insulin levels and HOMA-IR indices which is consistent with the studies on Zucker Fatty fa/fa or Zucker Diabetic Fatty fa/fa rats showing a reduction in blood glucose and/or plasma insulin levels [24,45,[47][48][49][50][51][52]54,55,59,62,64]. Further, the improved oral glucose tolerance in our RYGB rats is in line with previous studies in which it was evaluated [45,46,57,62].…”

Section: Discussionsupporting

confidence: 91%

“…These studies, however, like those in db/db mice [33,34], were not directly aimed at assessing the necessity of leptin receptors on the sustained weight loss and food intake suppression as well as improved glycemic control induced by RYGB, which is most likely why their details of food intake were either generally incomplete [44][45][46][47][48][49][50][51]54,61,62,64] or entirely missing [24,33,34,52,53,[55][56][57][58][59][60]63], and their study conclusions were unrelated to leptin. Our findings contrast with the studies showing a lack of sustained weight loss after RYGB [24,48,51,54,57,58,61,63], but are in line with the majority that do [45][46][47]49,50,52,55,59,62,64]. Further, our findings contrast with the study showing a lack of sustained food intake suppression induced by RYGB…”

Section: Discussionmentioning

confidence: 99%

“…Zucker Diabetic Fatty fa/fa rats, on the other hand, additionally harbor a mutation that reduces insulin promoter activity in pancreatic beta cells [42], rendering them incapable of secreting adequate amounts of insulin and thus genuinely diabetic [43]. Numerous studies have been performed aimed at assessing the metabolic effects of RYGB on both Zucker Fatty fa/fa [44][45][46][47][48] and Zucker Diabetic Fatty fa/fa [24,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] rats, but their descriptions on food intake were generally either incomplete [44][45][46][47][48][49][50][51]54,61,62,64] or, in many studies, entirely missing [24,52,53,[55][56][57][58][59][60]63]. Additionally, only a few of these studies incorporated a lean control group...…”

Section: Introductionmentioning

confidence: 99%

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Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery

Hankir¹,

Rotzinger²,

Nordbeck³

et al. 2021

Preprint

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Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of endogenous leptin action. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery

Hankir¹,

Rotzinger²,

Nordbeck³

et al. 2021

Preprint

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“…Excess intracellular lipids and dysfunctional insulin receptor signaling leads to blunted expression of mitochondrial genes, including the master mitochondrial biogenesis transcriptional regulator peroxisome proliferator-activated receptor co-activator 1 alpha (PCG1α) (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery

Barberio

Dohm

Pories

et al. 2021

Preprint

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Roux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) which can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes.MethodsVastus lateralis biopsy transcriptomes were generated pre- and 1-yr post-RYGB in black adult females with (T2D; n = 5, age=51±6 yr, BMI=53.0±5.8 kg/m2) and without (CON; n = 7,43±6 yr,51.0±9.2 kg/m2) T2DM. Insulin, glucose, and HOMA-IR were measured in blood at the same time points. ANCOVA detected differentially expressed genes (p< 0.01, Fold change<|1.2|), which were used to identify enriched biological pathways.ResultsPre-RYGB, 95 probes were downregulated with T2D including subunits of mitochondrial complex I. Post-RYGB, the T2D group had normalized gene expression when compared to their non-diabetic counterparts with only 3 probes remaining significantly different. In the T2D, we identified 52 probes upregulated from pre- to post-RYGB, including NDFUB7 and NDFUA1.ConclusionBlack females with T2DM show extensive down regulation of genes across aerobic metabolism pathways prior to RYGB, which resolves 1 year post-RYGB and is related to improvements in clinical markers. These data support efficacy of RYGB for improving skeletal muscle health, especially in patients with T2DM.

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Metabolic effects of duodenojejunal bypass surgery in a rat model of type 1 diabetes

et al. 2020

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Gastric Bypass Surgery Improves the Skeletal Muscle Ceramide/S1P Ratio and Upregulates the AMPK/ SIRT1/ PGC-1α Pathway in Zucker Diabetic Fatty Rats

Cited by 15 publications

References 51 publications

Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery

Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery

Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery

Metabolic effects of duodenojejunal bypass surgery in a rat model of type 1 diabetes

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